Polymer brush coated iron oxide nanoparticles for biomedical applications

Abstract

In recent years, the use of iron oxide nanoparticles has gained importance for biological applications such as hyperthermia, targeted drug delivery, drug release, bioseparation, bio-imaging etc. since they are mono-disperse, biocompatible and more importantly they have magnetic properties. In this thesis, water dispersible, monodisperse, disulfide-containing thiol reactive iron oxide nanoparticles have been synthesized. The disulfide groups were introduced either close to nanoparticle surface or on the exterior of the polymeric coating. Additionally, for surface functionalized polymer brush coated nanoparticles, NHS activated carboxylic acid functionalized were also introduced to enable non-cleavable functionalization using molecules containing amine groups. For the synthesis of such functional molecules, chain transfer agent with/without disulfide bond that is used for RAFT polymerization was modified with catechol anchoring group. These compounds were immobilized onto oleic acid stabilized iron oxide nanoparticles via ligand-exchange reaction. PEG based polymers were grafted from the surface of iron oxide nanoparticles by RAFT polymerization in order to make them water dispersible. The end groups of these polymers are trithiocarbanate groups, which can be modified by azo initiators by radical exchange reactions. For this reason, NHS activated carboxylic acid and disulfide functionalized azo initiators were synthesized and used for the functionalization of grafted polymers. After functionalization of polymer-coated iron oxide nanoparticles, they were able to react with thiol and amine bearing molecules. By using the same chemistry methods, disulfide bearing chain transfer agents were immobilized onto the nanoparticles and PEG based polymers were grown from the surface of nanoparticles by RAFT polymerization and grafting-from approach. Disulfide bearing polymers were cleaved from oxide nanoparticles by using reducing agents. Additionally, this method provides an excellent way to measure the molecular weights of the polymers that are grown by grafting-from approach.